Mechanisms for anesthesia, unawareness, respiratory depression, memory replay and sleep: MHb > IPN > PAG + DRN + MRN > claustrum > cortical slow waves
arXiv Preprint Archive August 21, 2025 Karin Vadovičová
The author proposes a neural model in which the medial habenula (MHb) to interpeduncular nucleus (IPN) circuit promotes slow-wave sleep, memory replay, and rest, while inhibiting awareness, arousal, and REM sleep. Activation of this circuit by mu-opioids, anesthetics, and other substances slows respiration and heart rate. The model also explains how ketamine and psychedelics may produce anxiolytic and antidepressant effects by activating 5-HT2a receptors in the IPN, claustrum, and infralimbic cortex, increasing feelings of safety and cognitive flexibility while attenuating fear and impulsivity.